NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

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@article{6e4fd1975bdc4723bdab7894920dd358,
title = "NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage",
abstract = "Glutamate receptor subunit 4 (GluA4) is highly expressed by neural cells sensitive to excitotoxicity, and is the predominant subunit expressed by oligodendrocyte precursor cells (OPC) during a key period of vulnerability to hypoxic-ischemic injury. Therefore, transcriptional networks downstream of excitotoxic GluA4 activation represent a promising area for therapeutic intervention. In this work, we identify the CCAAT binding transcription factor NF-Yb as a novel transcriptional regulator of Gria4 (GluA4 gene), and a controller of excitotoxic death in the oligodendroglial lineage. We describe a novel regulatory region within Gria4 containing CCAAT sequences whose binding by NF-Yb is regulated by excitotoxicity. Excitotoxicity-induced alterations in NF-Yb binding are associated with changes in Gria4 transcription, while knockdown of NF-Yb alters the transcription of reporter constructs containing this regulatory region. Data from immortalised and primary OPC reveal that RNAi and pharmacological disruption of NF-Yb alter Gria4 transcription, with the latter inducing apoptosis and influencing a set of apoptotic genes similarly regulated during excitotoxicity. These data provide the first definition of a trans-acting mechanism regulating Gria4, and identify the NF-Y network as a potential source of pharmacological targets for promoting OPC survival.",
keywords = "AMPA receptor, CCAAT, Excitotoxicity, GluA4, Gria4, NF-Yb, Oli-neu, Oligodendrocyte precursor cell, Transcriptional regulation",
author = "Ghazala Begum and Masahiro Otsu and Usman Ahmed and Zubair Ahmed and Adam Stevens and Daniel Fulton",
year = "2018",
month = apr,
day = "27",
doi = "10.1002/glia.23446",
language = "English",
journal = "GLIA",
issn = "0894-1491",
publisher = "Wiley",

}

RIS

TY - JOUR

T1 - NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

AU - Begum, Ghazala

AU - Otsu, Masahiro

AU - Ahmed, Usman

AU - Ahmed, Zubair

AU - Stevens, Adam

AU - Fulton, Daniel

PY - 2018/4/27

Y1 - 2018/4/27

N2 - Glutamate receptor subunit 4 (GluA4) is highly expressed by neural cells sensitive to excitotoxicity, and is the predominant subunit expressed by oligodendrocyte precursor cells (OPC) during a key period of vulnerability to hypoxic-ischemic injury. Therefore, transcriptional networks downstream of excitotoxic GluA4 activation represent a promising area for therapeutic intervention. In this work, we identify the CCAAT binding transcription factor NF-Yb as a novel transcriptional regulator of Gria4 (GluA4 gene), and a controller of excitotoxic death in the oligodendroglial lineage. We describe a novel regulatory region within Gria4 containing CCAAT sequences whose binding by NF-Yb is regulated by excitotoxicity. Excitotoxicity-induced alterations in NF-Yb binding are associated with changes in Gria4 transcription, while knockdown of NF-Yb alters the transcription of reporter constructs containing this regulatory region. Data from immortalised and primary OPC reveal that RNAi and pharmacological disruption of NF-Yb alter Gria4 transcription, with the latter inducing apoptosis and influencing a set of apoptotic genes similarly regulated during excitotoxicity. These data provide the first definition of a trans-acting mechanism regulating Gria4, and identify the NF-Y network as a potential source of pharmacological targets for promoting OPC survival.

AB - Glutamate receptor subunit 4 (GluA4) is highly expressed by neural cells sensitive to excitotoxicity, and is the predominant subunit expressed by oligodendrocyte precursor cells (OPC) during a key period of vulnerability to hypoxic-ischemic injury. Therefore, transcriptional networks downstream of excitotoxic GluA4 activation represent a promising area for therapeutic intervention. In this work, we identify the CCAAT binding transcription factor NF-Yb as a novel transcriptional regulator of Gria4 (GluA4 gene), and a controller of excitotoxic death in the oligodendroglial lineage. We describe a novel regulatory region within Gria4 containing CCAAT sequences whose binding by NF-Yb is regulated by excitotoxicity. Excitotoxicity-induced alterations in NF-Yb binding are associated with changes in Gria4 transcription, while knockdown of NF-Yb alters the transcription of reporter constructs containing this regulatory region. Data from immortalised and primary OPC reveal that RNAi and pharmacological disruption of NF-Yb alter Gria4 transcription, with the latter inducing apoptosis and influencing a set of apoptotic genes similarly regulated during excitotoxicity. These data provide the first definition of a trans-acting mechanism regulating Gria4, and identify the NF-Y network as a potential source of pharmacological targets for promoting OPC survival.

KW - AMPA receptor

KW - CCAAT

KW - Excitotoxicity

KW - GluA4

KW - Gria4

KW - NF-Yb

KW - Oli-neu

KW - Oligodendrocyte precursor cell

KW - Transcriptional regulation

UR - http://epapers.bham.ac.uk/3088/

U2 - 10.1002/glia.23446

DO - 10.1002/glia.23446

M3 - Article

AN - SCOPUS:85046020802

JO - GLIA

JF - GLIA

SN - 0894-1491

ER -